Wang Mengjie, Bai Yu, Pei Jiaxin, Li Dongqing, Pu Xiaolin, Zhu Wenyu, Xia Lei, Qi Chunjian, Jiang Hua, Ning Yongling
Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People's Hospital, Changzhou, China.
Medical Research Center, The Affiliated Hospital of Nanjing Medical University, Changzhou No. 2 People's Hospital, Changzhou, China.
Front Pharmacol. 2022 Apr 25;13:887457. doi: 10.3389/fphar.2022.887457. eCollection 2022.
Programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) checkpoint blocking antibodies have been shown to be a powerful immune checkpoint blockade (ICB) therapy for patients with cancer. However, patients quickly develop resistance to immunotherapy. β-glucan, an immune adjuvant, has been found to stimulate innate and adaptive immune responses. In this study, we assessed the use of whole glucan particle (WGP) β-glucan in combination with PD-1/PD-L1-blocking antibodies to slow down the resistance to immunotherapy. Results from a tumor mouse model demonstrated that administration of WGP β-glucan plus PD-1/PD-L1-blocking antibodies led to increased recruitment of immune-associated cells, improved regulation of the balance between T-cell activation and immune tolerance, and delayed tumor progression. This combination therapy was also found to improve progression-free survival in patients with advanced cancer who had previously discontinued anti-PD-1/PD-L1 because of disease progression. These findings suggest that β-glucan could be used as an immune adjuvant to reverse anti-PD-1/PD-L1 resistance by regulating the immune system.
程序性死亡蛋白 1（PD - 1）/程序性死亡配体 1（PD - L1）检查点阻断抗体已被证明是一种对癌症患者有效的免疫检查点阻断（ICB）疗法。然而，患者会迅速对免疫疗法产生耐药性。β - 葡聚糖作为一种免疫佐剂，已被发现可刺激先天性和适应性免疫反应。在本研究中，我们评估了全葡聚糖颗粒（WGP）β - 葡聚糖与 PD - 1/PD - L1 阻断抗体联合使用以减缓对免疫疗法的耐药性。肿瘤小鼠模型的结果表明，给予 WGPβ - 葡聚糖加 PD - 1/PD - L1 阻断抗体可导致免疫相关细胞的募集增加，改善 T 细胞活化与免疫耐受之间平衡的调节，并延缓肿瘤进展。还发现这种联合疗法可改善先前因疾病进展而停用抗 PD - 1/PD - L1 的晚期癌症患者的无进展生存期。这些发现表明，β - 葡聚糖可作为一种免疫佐剂，通过调节免疫系统来逆转抗 PD - 1/PD - L1 耐药性。
